Project #3 explores the transport of iron, manganese, cadmium and lead from environments experienced by children to the blood and critical organs like the brain, heart, liver, and kidney. We seek to better understand metal exposures of children and their mothers in settings like Tar Creek by (1) utilizing exposures during and after pregnancy, (2) using metal ions as well as complex environmental samples from Tar Creek, and (3) comparing different routes of entry from the environment into the body. Project 3 will also explore the role of toxic metals and iron status as they interact to influence metal absorption. In animal models, we will simultaneously study both the molecular mechanisms of metal transport as well as the corresponding pharmacokinetics of metals from the nose, lung and gut to the blood, central nervous system, and other organs. These data will be correlated with outcomes in both animal (Project 4) and human studies (Project 1). When data from Project 3 are combined with exposure assessment in Project 2, we will be able to better identify which routes of exposure result in the most significant body burdens of toxic metals. From this knowledge, we should be able to craft optimal strategies in Tar Creek to reduce the dose of toxic metals to mothers and children and thus better respond to the environmental concerns of the citizens in Tar Creek, Oklahoma.